The goal of this study is to understand the causes of abnormal skeletal growth in diabetes, somatotropin (GH) deficiency, and malnutrition. The study will require two stages. First, we will use stereologic methods (the body of mathematical methods relating the three dimensional parameters defining a structure to the two dimensional measurements obtainable on random sections of the structure) to develop a comprehensive, mathematical model of skeletal growth, including the levels of skeletal organization from whole bone to cell organelles and including the cell functions of proliferation and matrix synthesis. Quantitative autoradiography will be used to describe the cell proliferation for each cell type and cell synthesis of RNA, collagen, glycosaminoglycans, and proteoglycans. The rate of matrix synthesis and osteocyte transformation will be analyzed by use of tritiated proline topography. This model will be subjected to statistical analysis and make possible quantitative description of the relationships between cell structure and function and the relationships between cellular changes and skeletal growth. Second, we will develop mathematical models of skeletal growth in diabetes, malnutrition, and GH deficiency. We plan to use the models to identify the basic abnormalities responsible for poor skeletal growth in these three conditions. This information will advance understanding of normal skeletal growth and growth disorders, as well as provide a comprehensive mathematical model of skeletal growth. Based on these models of skeletal growth, we would develop a future proposal to determine in insulin-like growth factors (IGF), insulin, and GH can reverse the effects of GH deficiency, diabetes, and malnutrition on skeletal growth. Other future work based on this model could include investigation of the role of hormonal control on skeletal growth (e.g. parathoromone and vitamin D), studies of skeletal changes in prolonged corticosteroid adminstration, induced metabolic abnormalities, or impaired vascular or nerve supply.